The plasma membrane calcium pump: Functional domains, regulation of the activity, and tissue specificity of isoform expression

Carafoli, Ernesto; Stauffer, Thomas P.

doi:10.1002/neu.480250311

Cited by 129 publications

(77 citation statements)

References 76 publications

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“…Related mechanisms have been described in plant and animal plasma membrane Ca 2ϩ -ATPases, where either the N-terminal region (in the former case) or the C-terminal region (in the latter case) acts in an autoinhibitory fashion. In both cases, calmodulin functions as a small regulatory protein, and the inhibition is reversed by kinase-mediated phosphorylation within the calmodulin binding domain of the ATPase (30).…”

Section: Discussionmentioning

confidence: 99%

Tandem Phosphorylation of Ser-911 and Thr-912 at the C Terminus of Yeast Plasma Membrane H+-ATPase Leads to Glucose-dependent Activation

Lecchi

Nelson

Allen

et al. 2007

Journal of Biological Chemistry

123

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In recent years there has been growing interest in the posttranslational regulation of P-type ATPases by protein kinasemediated phosphorylation. Pma1 H ؉ -ATPase, which is responsible for H ؉ -dependent nutrient uptake in yeast (Saccharomyces cerevisiae), is one such example, displaying a rapid 5-10-fold increase in activity when carbon-starved cells are exposed to glucose. Activation has been linked to Ser/Thr phosphorylation in the C-terminal tail of the ATPase, but the specific phosphorylation sites have not previously been mapped. The present study has used nanoflow high pressure liquid chromatography coupled with electrospray electron transfer dissociation tandem mass spectrometry to identify Ser-911 and Thr-912 as two major phosphorylation sites that are clearly related to glucose activation. In carbon-starved cells with low Pma1 activity, peptide 896 -918, which was derived from the C terminus upon Lys-C proteolysis, was found to be singly phosphorylated at Thr-912, whereas in glucose-metabolizing cells with high ATPase activity, the same peptide was doubly phosphorylated at Ser-911 and Thr-912. Reciprocal 14 N/ 15 N metabolic labeling of cells was used to measure the relative phosphorylation levels at the two sites. The addition of glucose to carbon-starved cells led to a 3-fold reduction in the singly phosphorylated form and an 11-fold increase in the doubly phosphorylated form. These results point to a mechanism in which the stepwise phosphorylation of two tandemly positioned residues near the C terminus mediates glucose-dependent activation of the H ؉ -ATPase. Pma1 H ϩ

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Section: Discussionmentioning

confidence: 99%

Tandem Phosphorylation of Ser-911 and Thr-912 at the C Terminus of Yeast Plasma Membrane H+-ATPase Leads to Glucose-dependent Activation

Lecchi

Nelson

Allen

et al. 2007

Journal of Biological Chemistry

123

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“…In a manner similar to SERCA, the PMCA is an ATP-driven pump which moves Ca 2+ against its concentration gradient, thus functioning as an important system involved in maintaining low levels of cytoplasmic Ca 2+ . In mammals, four separate genes encode for the major PMCA isoforms (PMCA1 through 4) and the various gene products and splice variants which arise thereof show different patterns of expression during development as well as in different tissue beds [28,52]. While each isoform and splice variant can be regulated by multiple kinases and protein-protein interactions, the main regulator of PMCA function is Ca 2+ -bound Calmodulin (CaM) [131].…”

Section: Role Of Pmcamentioning

confidence: 99%

The non-excitable smooth muscle: Calcium signaling and phenotypic switching during vascular disease

House

Potier

Bisaillon

et al. 2008

Pflugers Arch - Eur J Physiol

221

207

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Calcium (Ca 2+ ) is a highly versatile second messenger that controls vascular smooth muscle cell (VSMC) contraction, proliferation, and migration. By means of Ca 2+ permeable channels, Ca 2+ pumps and channels conducting other ions such as potassium and chloride, VSMC keep intracellular Ca 2+ levels under tight control. In healthy quiescent contractile VSMC, two important components of the Ca 2+ signaling pathways that regulate VSMC contraction are the plasma membrane voltageoperated Ca 2+ channel of the high voltage-activated type (L-type) and the sarcoplasmic reticulum Ca 2+ release channel, Ryanodine Receptor (RyR). Injury to the vessel wall is accompanied by VSMC phenotype switch from a contractile quiescent to a proliferative motile phenotype (synthetic phenotype) and by alteration of many components of VSMC Ca 2+ signaling pathways. Specifically, this switch that culminates in a VSMC phenotype reminiscent of a non-excitable cell is characterized by loss of L-type channels expression and increased expression of the low voltage-activated (T-type) Ca 2+ channels and the canonical transient receptor potential (TRPC) channels. The expression levels of intracellular Ca 2+ release channels, pumps and Ca 2+ -activated proteins are also altered: the proliferative VSMC lose the RyR3 and the sarcoplasmic/endoplasmic reticulum Ca 2+ ATPase isoform 2a pump and reciprocally regulate isoforms of the ca 2+ /calmodulin-dependent protein kinase II. This review focuses on the changes in expression of Ca 2+ signaling proteins associated with VSMC proliferation both in vitro and in vivo. The physiological implications of the altered expression of these Ca 2+ signaling molecules, their contribution to VSMC dysfunction during vascular disease and their potential as targets for drug therapy will be discussed.

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“…Mammalian PMCAs are encoded by a multigene family consisting of four members termed PMCA 1-4 (3). Additional isoform diversity is generated via alternative RNA splicing (3,4). Alternative splicing of the C-terminal tail has been shown to alter the regulatory properties of PMCA isoforms, particularly with respect to phosphorylation and calmodulin stimulation (5-10).…”

Section: Pump Isoforms Resemble Those Of Kmentioning

confidence: 99%

Plasma Membrane Ca2+ ATPase Isoform 4b Binds to Membrane-associated Guanylate Kinase (MAGUK) Proteins via Their PDZ (PSD-95/Dlg/ZO-1) Domains

Kim¹,

DeMarco²,

Marfatia³

et al. 1998

Journal of Biological Chemistry

152

139

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Plasma membrane Ca2؉ ATPases are P-type pumps important for intracellular Ca 2؉ homeostasis. The extreme C termini of alternatively spliced "b"-type Ca 2؉ pump isoforms resemble those of K ؉ channels and Nmethyl-D-aspartate receptor subunits that interact with channel-clustering proteins of the membrane-associated guanylate kinase (MAGUK) family via PDZ domains. Yeast two-hybrid assays demonstrated strong interaction of Ca 2؉ pump 4b with the PDZ1؉2 domains of several mammalian MAGUKs. Pump 4b and PSD-95 could be co-immunoprecipitated from COS-7 cells overexpressing these proteins. Surface plasmon resonance revealed that a C-terminal pump 4b peptide interacted with the PDZ1؉2 domains of hDlg with nanomolar affinity (K D ‫؍‬ 1.6 nM), whereas binding to PDZ3 was in the micromolar range (K D ‫؍‬ 1.2 M). In contrast, the corresponding C-terminal peptide of Ca 2؉ pump 2b interacted weakly with PDZ1؉2 and not at all with PDZ3 of hDlg. Ca 2؉ pump 4b bound strongly to PDZ1؉2؉3 of hDlg on filter assays, whereas isoform 2b bound weakly, and the splice variants 2a and 4a failed to bind. Together, these data demonstrate a direct physical binding of Ca 2؉ pump isoform 4b to MAGUKs via their PDZ domains and reveal a novel role of alternative splicing within the family of plasma membrane Ca 2؉ pumps. Alternative splicing may dictate their specific interaction with PDZ domain-containing proteins, potentially influencing their localization and incorporation into functional multiprotein complexes at the plasma membrane.Temporal and spatial control of intracellular Ca 2ϩ concentrations is essential for eukaryotic cell physiology. Plasma membrane Ca 2ϩ ATPases (PMCAs) 1 represent a ubiquitous, high affinity system for the expulsion of Ca 2ϩ from the cell and are thought to be responsible for the long-term setting and maintenance of intracellular Ca 2ϩ levels (1, 2). Mammalian PMCAs are encoded by a multigene family consisting of four members termed PMCA 1-4 (3). Additional isoform diversity is generated via alternative RNA splicing (3, 4). Alternative splicing of the C-terminal tail has been shown to alter the regulatory properties of PMCA isoforms, particularly with respect to phosphorylation and calmodulin stimulation (5-10). Many PMCA isoforms and splice variants are expressed in a tissueand cell type-specific manner (11-17), and in several cell types, the PMCA has been shown to be concentrated in specific membrane domains by immunocytochemical analyses. For example, in kidney and intestinal epithelia involved in transcellular Ca 2ϩ flux, the pump is generally localized to the basolateral membrane (18). Using immunoelectron microscopy, the PMCA was recently detected at the plasma membrane surrounding the soma, as well as in the dendrites and spines of cerebellar Purkinje cells where it co-localized with P-type Ca 2ϩ channels (19). Taken together, these studies indicate that different isoforms of the PMCA may play an active role in the local control of Ca 2ϩ signaling and the dynamic regulation of Ca 2ϩ microdomains (7,20). Howev...

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The plasma membrane calcium pump: Functional domains, regulation of the activity, and tissue specificity of isoform expression

Cited by 129 publications

References 76 publications

Tandem Phosphorylation of Ser-911 and Thr-912 at the C Terminus of Yeast Plasma Membrane H+-ATPase Leads to Glucose-dependent Activation

Tandem Phosphorylation of Ser-911 and Thr-912 at the C Terminus of Yeast Plasma Membrane H+-ATPase Leads to Glucose-dependent Activation

The non-excitable smooth muscle: Calcium signaling and phenotypic switching during vascular disease

Plasma Membrane Ca2+ ATPase Isoform 4b Binds to Membrane-associated Guanylate Kinase (MAGUK) Proteins via Their PDZ (PSD-95/Dlg/ZO-1) Domains

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